Pulmonary Fibrosis (PF) is a heterogeneous group of serious diseases characterized by excessive accumulation of collagen and other connective tissue components in the alveolar membrane. The mechanisms responsible for such accumulation are not known. In preliminary work from our laboratories we have demonstrated that lung organ cultures and lung fibroblasts obtained from PF patients display increased protein and collagen biosynthesis compared to normals. The purpose of the work proposed in this application will be to perform and in depth and exhaustive study of the mechanisms responsible for the connective tissue alterations displayed by PF lungs. Particular emphasis will be placed on the study of the regulation of collagen synthesis and degradation in PF cultured fibroblasts applying State of the Art technology employing biosynthetic and biochemical methods as well as recently developed recombinant DNA techniques currently used in our laboratories. We will measure levels of functional and translatable mRNA and the rates of intracellular degradation of collagen in these cells. We will also investigate the role of extra fibroblastic regulatory factors. Particular attention will be given to the interactions of mononuclear cells with fibroblasts. Biosynthesis of collagen in lung organ cultures and tissue cultures from lung fibroblasts will be examined and the biosynthesized products will be characterized. Differences in the content or structure of the various components present in the tissues or synthesized in the PF lung cultures will be identified. Special emphasis will be placed on the identification of the various collagen types present and in the quantitation of their relative proportions. Several other differences in the biological characteristics of normal and PF cells and tissues will be explored in further detail. It is expected that the knowledge gained from these studies will be of direct relevance to understand the pathogenesis of the excessive collagen deposition characteristic of PF and will permit a more rational approach to develop possible modes of therapy for these incurable and devasting diseases.